Dactolisib (BEZ235, NVP-BEZ235)

目录号:S1009

Dactolisib (BEZ235, NVP-BEZ235) Chemical Structure

Molecular Weight(MW): 469.55

Dactolisib (BEZ235, NVP-BEZ235) 是一种双重ATP竞争性 PI3KmTOR 抑制剂,在无细胞试验中,抑制 p110α/γ/δ/β 和 mTOR(p70S6K) 的 IC50 分别为 4 nM /5 nM /7 nM /75 nM /6 nM。 在 3T3TopBP1-ER 细胞中抑制 ATR,IC50 为 21 nM,而对 Akt 和 PDK1 的抑制作用很弱。Phase 2。

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RMB 1414.41 现货
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客户购买Selleck的此次产品后发表的文献82篇:

客户使用该产品的11个实验数据:

  • Level of phospho-proteins in RTK and PI3K–Akt–mTOR pathways in treated tumours, detected with western blot.

    Nature, 2017, 728-732. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

    Relative kinase activities of p110α mutants and the inhibitory effect of PI3K inhibitors against hotspot mutants of p110α. A, recombinant FLAG-tagged PI3K p110α/p85α protein complex produced in 293T cells was immunoprecipitated , and the immunoprecipitates were used for the quantitative PI3K-HTRF assay (32).

    B, effect of three PI3K inhibitors (ZSTK474, LY294002, and NVP-BEZ235) on the enzymatic activity of two hotspot mutants (E545K and H1047R) p110α compared with the wild-type. No striking difference was observed in the IC50 concentrations of these inhibitors between wild-type and mutant p110α.
     

     

    Cancer Res 2010 70, 4982-4994. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

  • A, ANOVA of IC50 values of the dual PI3K/mTOR inhibitor NVP-BEZ235 in 23 melanoma cell lines showing no significant difference in sensitivity to this compound in B-Raf mutant and Braf wild-type cells. B, decreases in pAkt and pP70S6K in a dose and time-dependent fashion in 2 melanoma cell lines treated with NVP-BEZ235. pP70S6K levels are undetectable at all concentrations and time points studied, whereas levels of pAkt start rising again after 4 hours of drug exposure in a dose-dependent fashion. C, clonogenic assays in 2 melanoma cell lines (YUVON and YUSIK) treated with NVP-BEZ235 at different concentrations. NVPBEZ235 was effective in inhibiting colony formation at low nanomolar concentrations.

    Clin Cancer Res 2010 16, 6029-6039. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

    Three-dimensional responses of MCF7/IGF-1R cells to TAM (1 μM), E2 and IGF-1. Compared to parental MCF7 cells (a), MCF7/IGF-1R cells (b) in three-dimensional (3D) culture formed bigger acini in response to IGF-1 stimulation and displayed significant TAM resistance when treated with TAM (1 μM) + E2 + IGF-1, which was removable by kinase inhibitors BMS-536924, U0126 and BEZ235 (c). Cells (10,000/well) were seeded in 96-well plates. Acini were formed on 100% Matrigel and cultured for 14 days in starving medium containing 2% Matrigel and 5% charcoal/dextran-stripped fetal bovine serum with the treatments as indicated. Concentrations used: TAM (1 μM), E2 (1 nM) and IGF-1 (100 ng/mL). Confocal image original magnification, × 20. Red, rhodamine phalloidin (actin). Blue, Hoechst blue stain. Results are representative of two individual experiments.

    Breast Cancer Res 2011 13, R52. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

  • TAM (10 nM) agonistic behavior in MCF7/IGF-1R cells is not inhibited by phosphatidylinositol 3-kinase/Akt inhibitor BEZ235. (a) Inhibitory effects of kinase inhibitors BMS-536924, U0126 and BEZ235 on agonistic effect of TAM (10 nM) in the presence of IGF-1 (100 ng/mL). **P < 0.01. (b) Inhibitory effects of phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor BEZ235 at various dose ranges on IGF-1R signaling. (c) Agonistic behavior of TAM (10 nM) in response to BEZ235 kinase inhibitor. (-), no BEZ235. Results are representative of three independent experiments. Data are expressed as means ± SD.

    Breast Cancer Res 2011 13:R52. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

    ZSTK474 and GDC-0941 selectively inhibit class I PI3K over mTOR. (A) Inhibition profiles of the selected five PI3K inhibitors for mTOR. Data shown are mean±SD (n = 3), representative of 2 or 3 independent experiments. (B) IC50 values of the PI3K inhibitors for mTOR. (C) Selectivity of each PI3K inhibitor for PI3Ka over mTOR. The selectivity index is expressed as the ratio of the IC50 value for mTOR over that for PI3Ka. The IC50 values of ZSTK474, NVP-BEZ235 and LY294002 for PI3Ka are 0.016, 0.007 and 0.6 μM, respectively, as reported previously by us.

     

     

    Eur J Cancer 2010 46, 1111-1121. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

  • (B) The effects of AZD2014, BEZ235, lapatinib, LEE011, pazopanib on PI3K/AKT signaling in sarcoma PDC line were determined by immunoblotting analysis. Cells were treated with 1 μM of the indicated drugs for 72 h.

    Transl Oncol, 2016, 9(3):197-202. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

    The effects of LY294002, rapamycin and NVP-BEZ235 on activation of PI3K-Akt-mTOR pathway in hepatocytes. (a) The mRNA expression (PI3K, Akt, mTOR, raptor) by Real-Time PCR, (b) protein expression (PI3K, Akt, mTOR, S6K) by ELISA kits; (c) protein expression of S6K and P-S6K by western blotting. The different letters indicated significant differences (P <0.05). LY = LY294002; rapa = rapamycin; NVP = NVP-BEZ235.

    Animal, 2016, 10(8):1319-27. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

  •  After starved in serum-free medium for 24h,breast cancer cells incubated with the indicated concentrations of BEZ235 for 3h,followed by 20-minute  stimulation of 100ng/ml EGF.

     

     

     

    Dr. Zhang of Tianjin Medical University. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

    After starved in serum-free medium for 24h,breast cancer cells incubated with the indicated concentrations of BEZ235 for 3h,followed by 20-minute  stimulation of 100ng/ml EGF.

     

     

    Dr. Zhang of Tianjin Medical University. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

  •  

    FIG. 4. Phospholipase A2 group 4A (PLA2G4A) expression was increased after BEZ235 treatment in basal-like xenografts. The bar graph shows the quantification of the immunoblots (mean±SD). PLA2G4A, Ethanolamine kinase 1 and 2 (ETNK1/2), Choline kinase alpha/beta (ChoKA/B), and β-actin protein expression were examined by immunoblotting of tissue samples after MRS experiments [control group (n= 5) and BEZ235-treated group (n=7)]. This demonstrated a higher expression of PLA2G4A protein ( P=0.005), but no changes in ETNK1 and ChoKA/B in samples from basal-like xenografts treated with BEZ235.

    Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

产品安全说明书

PI3K抑制剂选择性比较

生物活性

产品描述 Dactolisib (BEZ235, NVP-BEZ235) 是一种双重ATP竞争性 PI3KmTOR 抑制剂,在无细胞试验中,抑制 p110α/γ/δ/β 和 mTOR(p70S6K) 的 IC50 分别为 4 nM /5 nM /7 nM /75 nM /6 nM。 在 3T3TopBP1-ER 细胞中抑制 ATR,IC50 为 21 nM,而对 Akt 和 PDK1 的抑制作用很弱。Phase 2。
靶点
p110α [1]
(Cell-free assay)
p110γ [1]
(Cell-free assay)
mTOR (p70S6K) [1]
(Cell-free assay)
p110δ [1]
(Cell-free assay)
ATR [8]
(3T3TopBP1-ER cells)
4 nM 5 nM 6 nM 7 nM 21 nM
体外研究

BEZ235显著降低mTOR活化的激酶p70S6K的磷酸化水平。BEZ235导致S235/S236P-RPS6水平减少,IC50为6.5 nM。BEZ235抗mTOR的活性使用生化mTOR K-LISA试验测定,IC50为20.7 nM。BEZ235对其β旁系同源物的活性稍弱,IC50为75 nM。在人肿瘤细胞中,PI3K/Akt/mTOR通路经常被组成性活化。BEZ235阻断PI3K和mTOR激酶活性,通过结合于这些酶的ATP结合槽发挥作用。用逐渐增加浓度BEZ235处理PTEN-null细胞系PC3M和U87MG时,导致细胞增殖剂量依赖性减少,平均GI50为10-12 nM。[1] BEZ235是一种mTORC1/2催化抑制剂。[2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Trypanosoma brucei brucei MlnmRY51cW2rY4LvZolidCCDc4PhfS=> Mkm5NVghcA>? M2jXUGROW09? MkHjRY51cXS{eYDhco9{d22jbDDhZ5Rqfmm2eTD3bZRpKEWFNUCgc4YhOC5yMEK1JO69VQ>? MnyyNlQ5ODV7NE[=
MCF7 NXXYOVc{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{jyNVAvODFvMUCwJO69VQ>? NXzUe4N[PDhiaB?= Mn\PSG1UVw>? M4HWS2lEPTB;MD63N{DPxE1? NFLK[GszOzh5MUmwOC=>
HCT116 NUfFR2pJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGH1W5oxNjBzLUGwNEDPxE1? NGLIOHg1QCCq NFT0Xo1FVVOR M3y2W2lEPTB;MT6xOkDPxE1? M1y2TlI{QDdzOUC0
U87MG M1rSZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUiwMlAyNTFyMDFOwG0> NYLERZZZPDhiaB?= MVfEUXNQ M3zMZmlEPTB;MT6zNkDPxE1? M2q5O|I{QDdzOUC0
HBC4 M1\hWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWPafWk5OC5yMT2xNFAh|ryP NYi4ZlVyPDhiaB?= NYfW[HI5VG:pIFfJOVA:NThwNkGgUS=> NYDSRZE3OjJ|M{[yOFY>
BSY1 NX3ofJh{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NICzU2MxNjBzLUGwNEDPxE1? MXy0PEBp NG[4SIFNd2diR1m1NF0uQC52ODDN MViyNlM{PjJ2Nh?=
HBC5 M2\Ebmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFj4UnIxNjBzLUGwNEDPxE1? MYm0PEBp MnXZUI9oKEeLNUC9MVcvQDdiTR?= NW\IOlduOjJ|M{[yOFY>
MCF7 Mnv3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoHENE4xOS1zMECg{txO M{X2OlQ5KGh? MUPMc4chT0l3ME2tPE4yPiCP MlTCNlI{OzZ{NE[=
MDA-MB-231 NELDVWlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIO5NXQxNjBzLUGwNEDPxE1? NGP5SY81QCCq M4rpPGxw\yCJSUWwQU05NjB7IF2= MmnDNlI{OzZ{NE[=
U251 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1uzN|AvODFvMUCwJO69VQ>? M4PhPVQ5KGh? NH:0VlZNd2diR1m1NF0uPy54NjDN M1TRWlIzOzN4MkS2
SF268 NGfnb29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWO0dnZUOC5yMT2xNFAh|ryP NHH6ToI1QCCq MnTPUI9oKEeLNUC9MVcvQTJiTR?= MojuNlI{OzZ{NE[=
SF295 MmLlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlHBNE4xOS1zMECg{txO NVX6colZPDhiaB?= NWK4R2xIVG:pIFfJOVA:NThwM{GgUS=> MlexNlI{OzZ{NE[=
SF539 NYnBbYUyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmnVNE4xOS1zMECg{txO M{XvfFQ5KGh? MY\Mc4chT0l3ME2tPE42QSCP NUPtR2oxOjJ|M{[yOFY>
SNB75 NFvoeHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUGwMlAyNTFyMDFOwG0> MWi0PEBp MWXMc4chT0l3ME2tPE42QCCP NE\PN28zOjN|NkK0Oi=>
SNB78 NFPLSW9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkjxNE4xOS1zMECg{txO MY[0PEBp M3PVfmxw\yCJSUWwQU05NjZ3IF2= M2jablIzOzN4MkS2
HCC2998 NYrOV4NzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmG1NE4xOS1zMECg{txO M1v4c|Q5KGh? MULMc4chT0l3ME2tPE4xPSCP MmHBNlI{OzZ{NE[=
KM12 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3PZT|AvODFvMUCwJO69VQ>? MlzSOFghcA>? NGjmclJNd2diR1m1NF0uPy53NDDN NV\RcVRsOjJ|M{[yOFY>
HT-29 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWHDdVF[OC5yMT2xNFAh|ryP NGfPc441QCCq NVTYNml3VG:pIFfJOVA:NTdwN{WgUS=> MX:yNlM{PjJ2Nh?=
HCT15 NICyd29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmO2NE4xOS1zMECg{txO MXq0PEBp NEnJO4JNd2diR1m1NF0uQC5yMzDN NG[xWHkzOjN|NkK0Oi=>
HCT116 NXTTZ5c{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MorXNE4xOS1zMECg{txO NGnPN5E1QCCq NWXhXHpnVG:pIFfJOVA:NTdwNkGgUS=> MlrrNlI{OzZ{NE[=
NCI-H23 M1TkbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3;ReFAvODFvMUCwJO69VQ>? M{HlUVQ5KGh? MXzMc4chT0l3ME2tO{43PCCP NYfGSZp{OjJ|M{[yOFY>
NCI-H226 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGGyZokxNjBzLUGwNEDPxE1? M3f1RVQ5KGh? NXLRSWlVVG:pIFfJOVA:NThwNESgUS=> Mo\RNlI{OzZ{NE[=
NCI-H522 MmHaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{ToTlAvODFvMUCwJO69VQ>? NIrzdYw1QCCq NXP2NopTVG:pIFfJOVA:NThwNEWgUS=> Mo\NNlI{OzZ{NE[=
NCI-H438 M2ToOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3PJSVAvODFvMUCwJO69VQ>? NVTtfZg6PDhiaB?= NV\nS4R3VG:pIFfJOVA:NThwMUGgUS=> NGHtTGMzOjN|NkK0Oi=>
A549 M13CR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYewMlAyNTFyMDFOwG0> M{TIZ|Q5KGh? M{XndWxw\yCJSUWwQU05NjB5IF2= NVm3NY5POjJ|M{[yOFY>
DMS273 NYPoT3pRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlHONE4xOS1zMECg{txO NXnDTXB5PDhiaB?= MVfMc4chT0l3ME2tO{45OCCP MY[yNlM{PjJ2Nh?=
DMS114 M1L2cmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2ThSFAvODFvMUCwJO69VQ>? MV[0PEBp NF7BbFlNd2diR1m1NF0uQC5|OTDN M3LvNVIzOzN4MkS2
LOXIMVI NWPRRlJxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4ThelAvODFvMUCwJO69VQ>? NULlO4lzPDhiaB?= MWjMc4chT0l3ME2tPE43PiCP NWXRO|hjOjJ|M{[yOFY>
OVCAR3 NIraeZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoP6NE4xOS1zMECg{txO NWXkVIZsPDhiaB?= MV;Mc4chT0l3ME2tPE4yPyCP M2ny[|IzOzN4MkS2
OVCAR4 NXfGVoQyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFTjWHoxNjBzLUGwNEDPxE1? NUDqRmxwPDhiaB?= MoTBUI9oKEeLNUC9MVgvPThiTR?= MnPONlI{OzZ{NE[=
OVCAR5 NIXTXWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmKzNE4xOS1zMECg{txO NXiwNJFFPDhiaB?= MnH0UI9oKEeLNUC9MVcvPTdiTR?= Mmq5NlI{OzZ{NE[=
OVCAR8 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX7IWoF6OC5yMT2xNFAh|ryP MXG0PEBp MmfQUI9oKEeLNUC9MVcvQDRiTR?= NXjTTWRTOjJ|M{[yOFY>
SKOV3 NY\hR2g4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml3wNE4xOS1zMECg{txO MVS0PEBp M{Wxe2xw\yCJSUWwQU05NjRzIF2= NHTNWnEzOjN|NkK0Oi=>
RXF631L MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXm3R2ozOC5yMT2xNFAh|ryP NUjFclB[PDhiaB?= MWrMc4chT0l3ME2tPE4zOSCP NGC0R5kzOjN|NkK0Oi=>
ACHN NEjGVmRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXHXTmppOC5yMT2xNFAh|ryP MlTCOFghcA>? NGXpSpVNd2diR1m1NF0uPy57NTDN NF3OcGUzOjN|NkK0Oi=>
St-4 NV3NXJc6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn;6NE4xOS1zMECg{txO NViyb4RmPDhiaB?= Mk\5UI9oKEeLNUC9MVcvPDdiTR?= NVTlc45VOjJ|M{[yOFY>
MKN1 NHzpTmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1u1[FAvODFvMUCwJO69VQ>? NE\aeZY1QCCq NULmXW9oVG:pIFfJOVA:NThwNEGgUS=> M1rTUFIzOzN4MkS2
MKN7 MmTwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWSwMlAyNTFyMDFOwG0> NFG4XpM1QCCq NWTDPFdrVG:pIFfJOVA:NTdwNkigUS=> NGPCNFEzOjN|NkK0Oi=>
MKN28 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2jRVlAvODFvMUCwJO69VQ>? NIDSbGI1QCCq NIjieGhNd2diR1m1NF0uPy5yNzDN M4PUTFIzOzN4MkS2
MKN45 NELyUGZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIXxVVgxNjBzLUGwNEDPxE1? NV;zVG5SPDhiaB?= NH7PcnVNd2diR1m1NF0uQC5|NDDN NEjtUXAzOjN|NkK0Oi=>
MKN74 M{HYS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF3WenYxNjBzLUGwNEDPxE1? NXXsT2pEPDhiaB?= M1G3UGxw\yCJSUWwQU04NjR{IF2= MoPsNlI{OzZ{NE[=
DU145 NX;JUnBHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MViwMlAyNTFyMDFOwG0> NVnzbZNyPDhiaB?= NVvYPVdCVG:pIFfJOVA:NThwMU[gUS=> NG\sZVczOjN|NkK0Oi=>
PC3 M3zZbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2TWWVAvODFvMUCwJO69VQ>? M{PJdlQ5KGh? NVS0SoxWVG:pIFfJOVA:NThwNk[gUS=> NEXBXm0zOjN|NkK0Oi=>
Trypanosoma brucei brucei MUjGeY5kfGmxbjDBd5NigQ>? MXeyNFAhdk1? Mn\xNVIhcA>? Mo\USG1UVw>? NF;KVmZF\WO{ZXHz[UBqdiCyaH;zdIhwfGmmeXygbY5we2m2b3ygdIhwe3CqYYTlJIxmfmWu NIjCN48zPDhyNUm0Oi=>
Trypanosoma brucei brucei NH;ITGVHfW6ldHnvckBCe3OjeR?= NW\reZFOOThiaB?= MW\EUXNQ NEHUVmJKdmirYnn0bY9vKG:oIILlZ4VxfG:{LX3l[IlifGWmIHXu[I9kgXSxc3nzJIF{e2W|c3XkJIF{KGSnY4LlZZNmKGmwIITyZY5{\mW{cnnuJJVxfGGtZR?= NVjxZXI2OjR6MEW5OFY>
Trypanosoma brucei brucei NX;kOoN3TnWwY4Tpc44hSXO|YYm= MYeyNFAhdk1? NWXBem12OTJiaB?= MoXPSG1UVw>? NWXKXlZtTW[oZXP0JI9vKHOyaHnu[49ugWynaX6gcIV3\Wx? NITUWngzPDhyNUm0Oi=>
Trypanosoma brucei brucei M134Z2Z2dmO2aX;uJGF{e2G7 MVGyNFAhdk1? NX21UHhZOTJiaB?= MUXEUXNQ M3PEPWVn\mWldDDvckBxcG:|cHjheIllgWylaH;sbY5mKGyndnXs NWHSNFN1OjR6MEW5OFY>
UM-UC-3 MknSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1q3WmlEPTB;M{G1JJBO NIHDS3FUSU6JRWK=
SBC-1 NXzwVHZlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2PnXGlEPTB;N{SyJJBO M1;FcHNCVkeHUh?=
MKN1 M4[0fmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlHhTWM2OD1{Lkigcm0> Ml76V2FPT0WU
NCI-H720 NGDuZXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIL1T2FKSzVyPUOuOVchdk1? NH7TZVVUSU6JRWK=
BFTC-909 MkH3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWHJR|UxRTNwN{Ggcm0> M4[ybnNCVkeHUh?=
BPH-1 NIDFW2ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnHGTWM2OD12Lke2JI5O M2jOdnNCVkeHUh?=
PC-3 NX[4enh{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3;YV2lEPTB;NT6wPUBvVQ>? M2\EcXNCVkeHUh?=
AN3-CA MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M12xUmlEPTB;NT61OkBvVQ>? NYnYXZJrW0GQR1XS
HN M4\4eGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmHLTWM2OD13Lkm2JI5O M3;xXHNCVkeHUh?=
HCC2218 MkH1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVfWfHBmUUN3ME22MlYyKG6P NWnrTY5zW0GQR1XS
KP-4 M1;6VGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mlm4TWM2OD15IH7N Mn;qV2FPT0WU
LU-139 NXzCS4JYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXfJR|UxRTdwN{egcm0> NGLoNllUSU6JRWK=
ETK-1 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV7JR|UxRTdwOEigcm0> NXr1TnU3W0GQR1XS
Ramos-2G6-4C10 M3W2cGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX3JR|UxRThwNEmgcm0> M4mz[HNCVkeHUh?=
MHH-PREB-1 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkjTTWM2OD17LkGyJI5O NV72eVRvW0GQR1XS
DU-4475 MoXmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmHSTWM2OD17LkS0JI5O NWnQeYppW0GQR1XS
NCI-H1666 NHjxbm9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYHJR|UxRTlwN{Ggcm0> MoDDV2FPT0WU
CAMA-1 MkPuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1zyO2lEPTB;OT64JI5O NHHmTVhUSU6JRWK=
TYK-nu NFzYUmhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH;lWlZKSzVyPUmuPVQhdk1? MY\TRW5ITVJ?
MFE-280 NFfvboJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV3CeXUyUUN3ME25Mlk6KG6P NULLOXVjW0GQR1XS
A549 M{HWPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHyyXIJKSzVyPUGwMlE1KG6P M4jHUXNCVkeHUh?=
769-P M1LwSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIn6bFlKSzVyPUGwMlQ1KG6P NGrlXHNUSU6JRWK=
L-363 NXLuW2hNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NInsbHhKSzVyPUGwMlY6KG6P NXToR|RjW0GQR1XS
ES8 M3fiPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NECzT|hKSzVyPUGwMlkhdk1? NYDEOm5nW0GQR1XS
PA-1 NGSzRllIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVfJR|UxRTFzLkiyJI5O Mm\DV2FPT0WU
Mewo M1fic2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVfieHY6UUN3ME2xNU46QSCwTR?= MXrTRW5ITVJ?
HSC-3 NEC2UFhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoXXTWM2OD1zMj6yNUBvVQ>? MlLEV2FPT0WU
H4 NIjNTo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVXzNpBwUUN3ME2xNk43PyCwTR?= M2TsWnNCVkeHUh?=
BB65-RCC MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVjFOHN6UUN3ME2xNk44OiCwTR?= NEXSTWVUSU6JRWK=
NCI-H1793 M3KzV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWTJR|UxRTF{LkiyJI5O MXHTRW5ITVJ?
KARPAS-45 MnjGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVLJR|UxRTF|LkWxJI5O MmPyV2FPT0WU
GCT MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHLORnpKSzVyPUGzMlY5KG6P MV7TRW5ITVJ?
EoL-1 NYP2NVl5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEK1UHFKSzVyPUGzMlk{KG6P M3fvOXNCVkeHUh?=
LB2241-RCC NX7JPGN1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGT0RYVKSzVyPUG0MlAyKG6P NWmwSG5HW0GQR1XS
ES5 NHTRVGRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3\kUmlEPTB;MUSuO|Qhdk1? M3PGdnNCVkeHUh?=
LOXIMVI MoW1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWrJR|UxRTF2Lkm5JI5O MUjTRW5ITVJ?
COR-L105 M{m3Wmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3zZe2lEPTB;MUWuNFQhdk1? NFPWV2tUSU6JRWK=
P12-ICHIKAWA NFfQOIdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{XMS2lEPTB;MUWuNUBvVQ>? Mo\aV2FPT0WU
CHL-1 NHLBeXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYKxPGJrUUN3ME2xOU41PSCwTR?= NYDWS|FQW0GQR1XS
VMRC-RCZ MlH6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2\UemlEPTB;MUWuOlMhdk1? NYHzVIdKW0GQR1XS
HH MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVHJR|UxRTF3Lkegcm0> NHLQPGpUSU6JRWK=
NUGC-3 M3\1bmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4PV[2lEPTB;MU[uN|Qhdk1? M2C4eXNCVkeHUh?=
EGI-1 NHf5dZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVrJR|UxRTF4LkSzJI5O MYTTRW5ITVJ?
OS-RC-2 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYXJR|UxRTF4LkS3JI5O NFi5[lZUSU6JRWK=
MOLT-16 Mn;pS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1LOT2lEPTB;MUeuNVUhdk1? NWDCWVdwW0GQR1XS
NCI-H209 M1yxTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIe3WVBKSzVyPUG3MlI6KG6P M1mzTnNCVkeHUh?=
697 M3jmRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEXoWmJKSzVyPUG3MlQ{KG6P MkTrV2FPT0WU
D-56MG NGHHT2NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUnJR|UxRTF5Lk[5JI5O MkXzV2FPT0WU
VA-ES-BJ NEj4XIRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVjJR|UxRTF5LkizJI5O M{ThWnNCVkeHUh?=
EW-16 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF2zcYRKSzVyPUG4MlA1KG6P NHH5S2NUSU6JRWK=
HGC-27 NWq3UmJpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYXJR|UxRTF6LkC2JI5O MkPaV2FPT0WU
ES7 M{jmSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3;nXGlEPTB;MUiuNFkhdk1? Mni2V2FPT0WU
HuH-7 M2HmbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYHJR|UxRTF6LkSgcm0> NF7XNGNUSU6JRWK=
BCPAP NITreVRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlzmTWM2OD1zOD62OUBvVQ>? NUXseIhnW0GQR1XS
SW1710 MknlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnvlTWM2OD1zOD63NkBvVQ>? NXvhe5RNW0GQR1XS
IST-MEL1 NGOxSVBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2PacmlEPTB;MUiuO|chdk1? MnS0V2FPT0WU
SF295 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVPJR|UxRTF6LkmzJI5O NV\INphwW0GQR1XS
RPMI-7951 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHPlOlZKSzVyPUG5MlI5KG6P MkDMV2FPT0WU
SF126 NEnNO29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX75N|JIUUN3ME2xPU41OSCwTR?= NHOzPWdUSU6JRWK=
GAMG MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHPGdpJKSzVyPUG5MlQ5KG6P NF3ielBUSU6JRWK=
KNS-81-FD MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF23dWFKSzVyPUG5MlU1KG6P NGjPS25USU6JRWK=
RT-112 M4jpd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEnTe3NKSzVyPUG5MlY3KG6P MXTTRW5ITVJ?
DEL MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGLJUoVKSzVyPUKwMlQ6KG6P M4HY[nNCVkeHUh?=
CGTH-W-1 M4XWRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFuySpZKSzVyPUKwMlY{KG6P M1HLSXNCVkeHUh?=
HOS NFjkVWlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWDJR|UxRTJzLkC2JI5O MX\TRW5ITVJ?
ES4 NU\2OFQxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXPJR|UxRTJzLkC4JI5O MXjTRW5ITVJ?
RXF393 M{nwW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn65TWM2OD1{MT60OUBvVQ>? MVfTRW5ITVJ?
NCI-H2030 M1LLbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWrHRpN1UUN3ME2yNU42OiCwTR?= MoSxV2FPT0WU
YH-13 NWfDe5JkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NInMeIZKSzVyPUKxMlg5KG6P MlPJV2FPT0WU
HT-1080 NFSyXG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYTJR|UxRTJzLkmzJI5O M1vWcnNCVkeHUh?=
NCI-SNU-1 Mlf1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXPJR|UxRTJzLkm1JI5O MonqV2FPT0WU
G-402 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NG\BUmdKSzVyPUKyMlE3KG6P MVfTRW5ITVJ?
786-0 NEDWNIRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVvJR|UxRTJ{LkK5JI5O MkDkV2FPT0WU
ME-180 M3vscGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVjGdI0{UUN3ME2yNk41OyCwTR?= Moe5V2FPT0WU
NB69 NWXrUoVnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXXJR|UxRTJ{LkWzJI5O NEDIcXRUSU6JRWK=
J-RT3-T3-5 NHrlXIFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFTxN2xKSzVyPUKyMlk3KG6P NUjYZpJGW0GQR1XS
TGBC1TKB MnPES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1LSd2lEPTB;MkOuNFUhdk1? M{W4W3NCVkeHUh?=
SW780 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmPUTWM2OD1{Mz6xN{BvVQ>? MYPTRW5ITVJ?
MG-63 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXzJR|UxRTJ|LkS1JI5O Mn[1V2FPT0WU
BV-173 M4rydWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NU\UXHppUUN3ME2yN{45PyCwTR?= NUTCb|RPW0GQR1XS
CAL-51 NWTuR4FFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIfVTGlKSzVyPUKzMlg6KG6P NGHac5FUSU6JRWK=
A375 NWraeFdtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWDHZ2tnUUN3ME2yN{46OyCwTR?= NFfudVdUSU6JRWK=
MEL-HO M1n2Nmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NETSW2RKSzVyPUK0MlA1KG6P NGXWVHdUSU6JRWK=
EFO-27 NETDdZVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIi1SW1KSzVyPUK0MlM{KG6P NILOeJVUSU6JRWK=
Hs-578-T NYrxZWI{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV3hRWMxUUN3ME2yOE42QCCwTR?= NVvCZ45iW0GQR1XS
NBsusSR MmfwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4jIWWlEPTB;MkSuOkBvVQ>? NWj5eWt1W0GQR1XS
CTB-1 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoHyTWM2OD1{ND62O{BvVQ>? Mm\UV2FPT0WU
FTC-133 NXfte3BET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXqyW3dkUUN3ME2yOU4yKG6P MVHTRW5ITVJ?
MOLT-4 NIHPOXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWDJR|UxRTJ3LkGyJI5O NVu0[|ByW0GQR1XS
HO-1-N-1 NV\pcGl5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXjJR|UxRTJ3LkG1JI5O MnfKV2FPT0WU
ES3 M2j2S2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGfZe5JKSzVyPUK1MlIzKG6P NXjnPJRHW0GQR1XS
TI-73 NGfy[3FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2XvSGlEPTB;MkWuNlghdk1? MnvDV2FPT0WU
MPP-89 M2\x[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlmwTWM2OD1{NT6zNkBvVQ>? NYDZTJVnW0GQR1XS
KYSE-150 NXTsUpVLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlrBTWM2OD1{NT64PUBvVQ>? Ml7rV2FPT0WU
LXF-289 NFHMcFJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{nWWWlEPTB;Mk[uNFQhdk1? NFHQe3FUSU6JRWK=
SK-LU-1 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MknaTWM2OD1{Nj6xO{BvVQ>? NH25TGdUSU6JRWK=
HOP-92 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEfGVZpKSzVyPUK2MlQ5KG6P MXHTRW5ITVJ?
HuO9 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2nwZmlEPTB;Mk[uO|Yhdk1? NUPXS3JWW0GQR1XS
SW962 NInnXYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlPOTWM2OD1{Nj63OkBvVQ>? MXfTRW5ITVJ?
RS4-11 MlXNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NI\BXJpKSzVyPUK2MlkyKG6P M1Pnd3NCVkeHUh?=
NCI-H292 NIrJSFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NI\RdnlKSzVyPUK3JI5O NGT2ZYRUSU6JRWK=
DB MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGDpdolKSzVyPUK3MlM3KG6P MlrHV2FPT0WU
SW1088 MkTSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkOzTWM2OD1{OD6yPUBvVQ>? NIf6R|NUSU6JRWK=
A204 MnvxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVnJR|UxRTJ6LkS3JI5O NV7lNFdGW0GQR1XS
A3-KAW MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVzPXm5ZUUN3ME2yPE43PCCwTR?= M2fTeHNCVkeHUh?=
MV-4-11 M1TiXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX\JR|UxRTJ6Lkegcm0> MULTRW5ITVJ?
ES1 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFrDbFdKSzVyPUK4Mlg1KG6P MlzWV2FPT0WU
ONS-76 NVnKflFXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1z4V2lEPTB;MkmuNFUhdk1? NX\5co9[W0GQR1XS
D-263MG M3XiWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmjFTWM2OD1{OT6zOUBvVQ>? M1;Z[XNCVkeHUh?=
U-2-OS Mmi2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoDlTWM2OD1{OT61JI5O M37neHNCVkeHUh?=
T98G NGqxTFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1L6RmlEPTB;MkmuPFghdk1? Mmf0V2FPT0WU
GI-ME-N MkLsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV;qdJhRUUN3ME2yPU46OSCwTR?= MULTRW5ITVJ?
BHT-101 MmLJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MW\JR|UxRTNyLkC1JI5O M3ToU3NCVkeHUh?=
NOS-1 NWLEeGFHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXPwbIF1UUN3ME2zNE4yOiCwTR?= MVvTRW5ITVJ?
AsPC-1 NFPjN4hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoPPTWM2OD1|MD6yJI5O NIfROFJUSU6JRWK=
QIMR-WIL NHjwdIdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUTCfIZCUUN3ME2zNE43KG6P NH\EZ3JUSU6JRWK=
JVM-3 NF[yS45Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWrXSpF2UUN3ME2zNE45OyCwTR?= MVnTRW5ITVJ?
KU-19-19 NIHSPJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MknFTWM2OD1|MT6xN{BvVQ>? M1vnVXNCVkeHUh?=
OVCAR-8 NFXDS4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXTJR|UxRTNzLkK2JI5O NVi0WWt[W0GQR1XS
BEN MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1LQSmlEPTB;M{GuOlMhdk1? NFrnRnFUSU6JRWK=
BE-13 NFfTbGtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEfScHZKSzVyPUOxMlgzKG6P NFvsSHBUSU6JRWK=
EW-18 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWm3NXhqUUN3ME2zNU45PiCwTR?= NIHr[oFUSU6JRWK=
ECC10 NFf6RXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3[wTGlEPTB;M{GuPVUhdk1? M4X3ZnNCVkeHUh?=
CTV-1 MmXDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGXtcItKSzVyPUOyMlgzKG6P NUPSV4xxW0GQR1XS
COLO-800 MnfBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{jWXGlEPTB;M{KuPVIhdk1? NYLqT3BCW0GQR1XS
A2058 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml3xTWM2OD1|Mz6yOUBvVQ>? NWHIU3RyW0GQR1XS
VM-CUB-1 NX:0[HpxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4nsPGlEPTB;M{OuOFMhdk1? NX;U[oZJW0GQR1XS
Ca9-22 NXTofplnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1jRV2lEPTB;M{OuOVUhdk1? M1LxenNCVkeHUh?=
COLO-684 Mm\DS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIXHfphKSzVyPUOzMlU5KG6P NXP1Z4VFW0GQR1XS
RPMI-8226 NV3SPYdbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV2wN41oUUN3ME2zN{45OiCwTR?= M3HqNHNCVkeHUh?=
SK-NEP-1 NWHaeWEyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml;LTWM2OD1|ND6xOUBvVQ>? M1m0UnNCVkeHUh?=
Becker MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3zncmlEPTB;M{SuNlEhdk1? NUPFRnVRW0GQR1XS
NCI-H28 NHW1UnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3nL[GlEPTB;M{SuOFQhdk1? Mn33V2FPT0WU
CAL-120 MoDkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEDHUGFKSzVyPUO0MlczKG6P NXjtSVJpW0GQR1XS
MDA-MB-157 NG\VOIhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVzJR|UxRTN3LkSxJI5O NV\YeY9RW0GQR1XS
OVCAR-5 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWHJR|UxRTN3LkS3JI5O M2nNfHNCVkeHUh?=
LAMA-84 NITWRWdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUfjWWt2UUN3ME2zOU45PyCwTR?= MmDHV2FPT0WU
CAKI-1 NVPyeo9QT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml3nTWM2OD1|Nj60N{BvVQ>? M3PyTnNCVkeHUh?=
Daoy NXSzZYxDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVjJR|UxRTN4Lkegcm0> M{fQWXNCVkeHUh?=
CAL-62 M2qxfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1rqSWlEPTB;M{[uPFYhdk1? M{K1N3NCVkeHUh?=
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IST-SL1 M3;4W2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4f2dGlEPTB;MT60OFI1KM7:TR?= NXPkenlUW0GQR1XS
COLO-741 M{nsZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEX3dmtKSzVyPUGuOFk4PzFizszN M3;PdHNCVkeHUh?=
LU-65 MmmxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mm\kTWM2OD1zLk[yNlQ6KM7:TR?= NHfN[I1USU6JRWK=
NCI-H1304 NFjRN4hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlzITWM2OD1zLk[1OFk5KM7:TR?= MV7TRW5ITVJ?
KARPAS-299 Mlf3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFXwdIZKSzVyPUGuO|k1PzlizszN NYfDbmM3W0GQR1XS
NCI-H358 NYrQdXM{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV3aSWdIUUN3ME2xMlk2PTB|IN88US=> MWTTRW5ITVJ?
OAW-28 MofxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnzhTWM2OD1{LkC2PVE6KM7:TR?= NWe1e5VyW0GQR1XS
C8166 NGnOXlBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mm\tTWM2OD1{Lk[zN|kzKM7:TR?= NHrCRYlUSU6JRWK=
COLO-678 NWq1OINqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIHBXmhKSzVyPUKuPFM4PjhizszN MlPPV2FPT0WU
SK-N-DZ NILtR2NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH7hO|BKSzVyPUKuPFY{QDFizszN NYHtOW9VW0GQR1XS
NCI-H82 M1rxe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWHJR|UxRTJwOUCzOlkh|ryP MoXwV2FPT0WU
JVM-2 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWDJR|UxRTNwMEOxPFgh|ryP M1OyOXNCVkeHUh?=
SW1116 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIKxRVRKSzVyPUOuNFU1OTFizszN NIrD[2hUSU6JRWK=
MDA-MB-453 NVe3bXg{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnfJTWM2OD1|LkGwOFM6KM7:TR?= NVvpZXlwW0GQR1XS
Calu-6 Mki5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXPRUFhIUUN3ME2zMlE6QTdizszN MnvQV2FPT0WU
SHP-77 NXTMbZJUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4HRbmlEPTB;Mz61Nlgh|ryP NHrNbGxUSU6JRWK=
Capan-2 M3jpc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXfJR|UxRTRwM{K1PFEh|ryP NXfLe|hNW0GQR1XS
SW948 NET0TY1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUe0doFyUUN3ME20Mlc1Pzd7IN88US=> NX;nZ3dWW0GQR1XS
HDLM-2 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2fxe2lEPTB;NT6wO|czPSEQvF2= M4rZOXNCVkeHUh?=
LAN-6 MlrwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGT2TJFKSzVyPU[uNlE1QTVizszN MoPUV2FPT0WU
LU-135 NIPveHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmnmTWM2OD14LkSzNFc4KM7:TR?= NUXiO|d5W0GQR1XS
T84 Ml7BS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2rqfmlEPTB;Nj65PFY1KM7:TR?= M1vOV3NCVkeHUh?=
CAPAN-1 NGjaSnJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYXJR|UxRTdwNkKyN|Mh|ryP NHP0fpZUSU6JRWK=
SW1417 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYPPboJ7UUN3ME23MlkyPzNzIN88US=> NEnnU3pUSU6JRWK=
BALL-1 NVXHSJF6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXrJR|UxRThwNUC0NFkh|ryP NHjpZ3BUSU6JRWK=
HT-29 NUmxdGh1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1OwZWlEPTB;OT6wO|U6QSEQvF2= M1zNW3NCVkeHUh?=
C3A Ml3OS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFmzNFBKSzVyPUmuPFg{QTRizszN MoWzV2FPT0WU
NCI-H1993 NU\O[WFKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIPqSZpKSzVyPUGwMlUxQDFizszN M{e2NnNCVkeHUh?=
SK-MEL-1 MlXuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1LBTGlEPTB;MUGuOlI5QSEQvF2= MnizV2FPT0WU
DU-145 NIKzSG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYniUXFqUUN3ME2xOE42ODV{IN88US=> NVrySmZ6W0GQR1XS
KP-N-YN NGm2ZWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWPJR|UxRTF2LkWxNFMh|ryP NHzFfHBUSU6JRWK=
CCRF-CEM M1O4WWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEC4U5VKSzVyPUG0Mlc5ODlizszN M4TqOXNCVkeHUh?=
ZR-75-30 MnvtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{ThdGlEPTB;MU[uN|MxOyEQvF2= M1T4c3NCVkeHUh?=
A673 M1mx[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV\HcpUxUUN3ME2yNE42PTB5IN88US=> MYfTRW5ITVJ?
K-562 M4jNT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmKwTWM2OD1{OD60NVg{KM7:TR?= NUDqN25HW0GQR1XS

... Click to View More Cell Line Experimental Data

体内研究 BEZ235诱导肿瘤(69%)消退,而对体重增加没有统计学上显著的作用。总之,这些初步的体内功效研究结果表明,BEZ235单一口服给药时能够阻断疾病的发展,与其他抗癌药结合使用时能够增强疗效。[1]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:

[2]

+ 展开

体外蛋白激酶,PI3K,和mTOR实验:

PI3Kα, β, δ蛋白都由与p110全长蛋白相接的p85 N端的iSH2域组成,只是PI3Kα没有最后的20个氨基酸。PI3Kγ由p110全长蛋白去掉前144个氨基酸产生而来。所有PI3K蛋白在羧基末端加组氨酸标签便于纯化,然后克隆到pBlue-Bac4.5 (用于α, β,和δ亚型) 或者pVL1393 (用于γ 亚型) 质粒中。转染BaculoGold WT基因组DNA的不同的载体按说明书推荐的方法生产各自重组体杆状病毒及重组蛋白。使用激酶发光检测试剂盒测定BEZ235 (NVP-BEZ235)作用于PI3K的活力。在384孔板上进行激酶实验。在每个孔中加入50 nl的测试项目(溶在90%DMSO中)和5ul的反应buffer,反应buffer包含10 μg/ml PI基质 (l-α-磷脂酰肌醇; 由Avanti Polar Lipids提供;预备在3%辛基葡萄糖苷中),然后加入PI3K 蛋白(p110α, p110β, p110δ,和p110γ分别为10, 25, 10,和150 nM)。加入预备在反应buffer中的5 ul 1 µM 的ATP反应开始,反应进行60分钟 (测p110α, p110β, p110δ)或者120分钟(测p110γ),随后加入10ul的荧光激酶buffer终止反应。数据用Synergy 2 阅读器阅读用于荧光测试。
细胞实验:

[1]

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  • Cell lines: HCT116, DLD-1, SW480
  • Concentrations: 0-1 μM
  • Incubation Time: 48小时
  • Method:

    HCT116 (PIK3CA突变型; 激酶域在H1047R), DLD-1 (PIK3CA突变型;螺旋域在E545K), SW480 (PIK3CA 野生型)人类CRC细胞系,同基因型的DLD-1 PIK3CA突变和野生型细胞培养在含10%FBS和1×青霉素/链霉素的培养基中。细胞按不同的初始密度加入(HCT116: 3000个细胞/每孔, DLD-1: 5500个细胞/每孔, SW480: 4500个细胞/每孔, DLD-1 PIK3CA突变型: 7000个细胞/每孔, DLD-1 PIK3CA野生型: 9000个细胞/每孔),用来计算不同的生长动力学。16个小时后,细胞加入浓度越来越高的BEZ235中进行温育,含有药物的培养基24小时更换一次。根据产品说明书,加入细胞16小时和药物处理48小时,使用单溶液细胞增殖检测试剂盒以比色法检测细胞活力。与没有用药物处理正在生长的细胞相比,药物处理的细胞的活力也逐渐趋于正常化。使用GraphPad Prism 5软件用4个参数的回归曲线计算IC50值。用于western blot 分析,细胞用0 nM 或者最高抑制剂量(500 nM) BEZ235处理 2, 6, 24, 或者48 小时。


    (Only for Reference)
动物实验:

[2]

+ 展开
  • Animal Models: 雌性Harlan无胸腺裸鼠
  • Formulation: NMP/聚乙二醇300(10/90,v/v)
  • Dosages: 45 mg/kg
  • Administration: 口服处理
    (Only for Reference)

溶解度 (25°C)

体外 DMF 18 mg/mL warmed (38.33 mM)
DMSO 0.01 mg/mL (0.02 mM)
Water Insoluble
体内 从左到右依次将纯溶剂加入产品,现配现用:
NMP+polyethylene glycol 300 (10+90, v+v)
30 mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 469.55
化学式

C30H23N5O

CAS号 915019-65-7
稳定性 powder
别名 N/A

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00620594 Completed Breast Cancer|Advanced Solid Tumors|Cowden Syndrome Novartis Pharmaceuticals|Novartis December 21, 2006 Phase 1
NCT01856101 Terminated Carcinoma Transitional Cell Cliniques universitaires Saint-Luc- Université Catholique de Louvain|Novartis February 2013 Phase 2
NCT01717898 Terminated Castrate-resistant Prostate Cancer Patients. Charles Ryan|Novartis Pharmaceuticals|University of California, San Francisco January 2013 Phase 1|Phase 2
NCT01658436 Completed Pancreatic Neuroendocrine Tumors (pNET) Novartis Pharmaceuticals|Novartis November 2012 Phase 2
NCT01628913 Terminated Pancreatic Neuroendocrine Tumors (pNET) Novartis Pharmaceuticals|Novartis October 2012 Phase 2
NCT01690871 Withdrawn Malignant PEComa (Perivascular Epithelioid Cell Tumors) Novartis Pharmaceuticals|Novartis September 2012 Phase 2

技术支持

在订购、运输、储存和使用我们的产品的任何阶段,您遇到的任何问题,均可以通过拨打我们的热线电话400-668-6834,或者技术支持邮箱tech@selleck.cn,直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题,请给我们留言。

  • * 必填项

常见问题及建议解决方法

  • 问题 1:

    With difficulties in dissolving BEZ235, How can I improve its solubility?

  • 回答:

    For in vivo study, we suggest the vehicle solution NMP/polyethylene glycol 300 (10/90, v/v). Please dissolve BEZ235 in NMP as more as possible. You can sonicate and warm it in water bath for a while. Then dilute with PEG 300.

PI3K Signaling Pathway Map

PI3K Inhibitors with Unique Features

相关PI3K产品

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID